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Background Skin adverse events associated with D-Penicillamine (DPA) are common and multi-faceted, although the presence of DPA or its metabolites has never been documented in the skin, because of inherent difficulties in determining its tissue levels. Thus, the association between DPA and DPA-related dermatoses has been only hypothesized on the basis of careful history, clinical observation and typical histopathological findings. Objective To detect DPA in biopsy specimens in a unique case of 25-year-late-onset elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum associated with a history of long-term high dose DPA, by applying a recently described analytical method to assess the presence of DPA in skin. Methods We used a reliable analytical method based on high-performance liquid chromatography coupled with amperometric detection to look for the presence of DPA in skin biopsy specimens. Results A chromatographic peak corresponding to DPA was evidenced in some affected skin samples collected from the patient. Conclusion We documented the effective presence and the persistence after 25 years of DPA in the skin of a woman affected by elastotic cutaneous change due to a long-term therapy with DPA. This report provides further evidence of the relationship between DPA deposit in affected skin and clinical manifestation.

Penicillamine (DL-2-amino-3-mercapto-3-methyl-butanoic acid) is a chelating agent derived from the hydrolysis of penicillin, lacking any antibiotic properties. The therapeutic form is D-penicillamine, while L-penicillamine is toxic. This drug is used in the treatment of severe active rheumatoid arthritis and acts by reducing the number of T-lymphocytes, inhibiting macrophage function and preventing collagen from cross-linking. It is also used as a chelating agent in Wilson's disease (a rare genetic disorder of copper metabolism), in cystinuria and in the treatment of heavy metal poisoning. Adverse effects are frequent and may include: membranous glomerulonephritis, antibody-mediated myasthenic syndrome, drug-induced systemic lupus erythematosus, toxic myopathies and elastosis perforans serpiginosa. This last one may persist even after the therapy withdrawal. Thus, to evaluate toxic effects in clinical cases we are developing a method based on capillary electrophoresis coupled to laser induced fluorescence detection (CE-LIF) in specific biological matrices such as epithelium. The analysis is carried out in a fused silica capillary, using a carbonate buffer as the background electrolyte. Satisfactory sensitivity was obtained by exciting the molecule at 488 nm after a derivatisation step with 5-(iodoacetamido)fluorescein (IAF). Preliminary results are promising and the validation of the method is in progress. At the same time, we are developing another technique based on reversed phase liquid chromatography with amperometric detection to analyse penicillamine in epithelium samples